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Chagas disease, caused by the protozoan parasite , remains a major public health problem, affecting approximately seven million people worldwide. Although historically restricted to endemic regions, migration has led to its global distribution, increasing the relevance of congenital transmission in non-endemic areas. If not timely diagnosed and treated, infection can progress to chronic Chagas cardiomyopathy in nearly 30 % of patients, generating substantial social and healthcare burdens. Diagnosis requires concordant results from two or three serological assays based on different antigenic principles, limiting timely access to care in peripheral settings. We aimed to characterize the clinical, parasitological, and sociodemographic profile of individuals with infection in La Matanza (Buenos Aires Province, Argentina), and to assess the diagnostic performance of two rapid diagnostic tests (RDTs) from serum samples in this at-risk population. In this cross-sectional prospective study including 103 subjects, epidemiological analysis revealed that most infected individuals originated from endemic areas, with a substantial proportion of infections consistent with congenital transmission. Clinical evaluation identified electrocardiographic abnormalities in 30.9 % of infected patients, predominantly right bundle branch block. Molecular characterization showed parasites belonging to DTU V (Discrete Typing Unit V) in 7 infections (one coinfected with DTU VI). RDT1 showed a sensitivity of 82.5 % and specificity of 100 %, whereas RDT2 exhibited a sensitivity of 87.5 % and specificity of 85.7 %. Overall, our findings provide a comprehensive characterization of infected individuals in a non-endemic region with ongoing transmission dynamics shaped by migration and congenital infection, pointing out advantages and limitations of RDT use in peripheral healthcare settings.

IntroductionChagas disease (CD) remains a major cause of cardiac and digestive morbidity and premature death in the Americas. Although benznidazole (BZN) and nifurtimox (NFX) are the only two available trypanocidal agents worldwide, direct comparisons between these two drugs in Brazilian adults are lacking. Therapeutic efficacy in chronically infected adults remains unclear as parasitological response is variable and serological negativisation is not frequent within short-term follow-up. Furthermore, the genetic diversity of Trypanosoma cruzi may influence treatment response and has been largely overlooked in clinical studies. The BENBRASIL trial aims to compare the efficacy and safety of BZN versus NFX in adults with chronic CD and to explore geographical variation in response to standard BZN treatment.Methods and analysisThe BENBRASIL trial is a multicentre, randomised, double-blind, double-dummy phase II superiority trial conducted in Brazil alongside a prospective observational cohort.A total of 150 adults with chronic indeterminate or mild cardiac forms of CD will be randomly allocated in a 1:1 ratio to receive standard BZN dose or NFX for 8 weeks in a double-blind, double-dummy placebo-controlled design and will be followed for 12 months. The primary endpoint is therapeutic efficacy defined as sustained parasitological response in PCR for parasitic DNA results for 12 months follow-up. Treatment failure will be defined as one confirmed PCR positivity, treatment discontinuation due to toxicity or death related to CD. Secondary outcomes include drug tolerability (including graded adverse events), treatment adherence and serological titres. The sample size (75 participants per arm) was calculated to provide approximately 80–85% power to detect a 25% absolute difference in sustained PCR negativity between groups at a two-sided α of 0.05. Additionally, a prospective observational cohort will enrol 300 additional participants receiving standard treatment of BZN to evaluate the effectiveness and safety of BZN across five epidemiological and geographical regions of Brazil representing distinct parasite genetic backgrounds. It aims to explore geographical variation in parasitological response within different discrete typing units using mixed-effects regression models adjusted for baseline covariates. The primary analysis will follow the intention-to-treat principle. For the primary endpoint, missing outcome data will be conservatively classified as treatment failure, with sensitivity analyses using multiple imputations. Recruitment began in March 2024.Ethics and disseminationThe protocol has been approved by Brazil’s National Research Ethics Committee and the institutional review boards of all participating centres. Written informed consent will be obtained from all participants. An independent Data Safety Monitoring Board will oversee safety outcomes. Study findings will be disseminated through peer-reviewed publications, scientific conferences and communication with national health authorities. Results may guide clinical practice and regulatory policies, strengthening therapeutic options for CD.Trial registration numberReBEC U1111-1287-7587. Date of registration: 06/07/2023 (https://ensaiosclinicos.gov.br/rg/RBR-973pt5n).

Leishmania (Leishmania) infantum zymodeme MON-1 is responsible for the majority of visceral leishmaniasis cases around the Mediterranean basin, albeit that it causes also cutaneous forms. The MON classification is based on starch gel multilocus enzyme electrophoresis (MLEE) typing. The aim of this work was to explore further the genetic diversity and phylogenetic status of this zymodeme by alternative typing techniques. Fourteen L. (L.) infantum/L. (L.) chagasi stocks identified as MON-1 by MLEE in reference laboratories, 3 L. infantum stocks attributed to other zymodemes (MON-24, MON-29, MON-33) and reference standard stocks belonging to other species (L. (L.) major, L. (L.) tropica and L. (L.) donovani) were characterized by 2 different markers: MLEE on cellulose acetate plates and Random Amplified Polymorphic DNA (RAPD). We have obtained 10 different genotypes with RAPD and 6 different genotypes with MLEE on cellulose acetate plates for the 14 L. infantum/L. chagasi MON-1 stocks studied. MLEE and RAPD data gave quite congruent phylogenetic results: L. infantum zymodeme MON-1 was shown to be polyphyletic and genetically heterogeneous. This work confirms the necessity of using different markers to build up a robust phylogeny. Finally the epidemiological and clinical implications of these results are discussed.

Chagas disease (CD), caused by Trypanosoma cruzi and endemic in Latin America, has become an emergent health problem in non-endemic countries due to human migration. The United States (US) is the non-Latin American country with the highest CD burden and cannot be considered as non-endemic, since triatomine vectors and reservoir animals have been found. Populations of T. cruzi are divided into genetic subdivisions, which are known as discrete typing units (DTUs): TcI to TcVI and TcBat. Autochthonous human T. cruzi infection in the US is sporadic, but it may change due to environmental factors affecting the geographic distribution of triatomines. We aimed to perform a literature review of the genetic diversity of T. cruzi in triatomine vectors and mammalian hosts, including human cases, in the US. The 34 analyzed studies revealed the presence of T. cruzi in 18 states, which was mainly concentrated in Texas, Louisiana and New Mexico. TcI and TcIV were the principal DTUs identified, being TcI the most genotyped (42.4%; 917/2164). This study represents a first attempt to compile the molecular epidemiology of T. cruzi in the US, which is fundamental for predicting the progression of the infection in the country and could be of great help in its future management.